Aberrant methylation of tumour suppressor genes WT1, GATA5 and PAX5 in hepatocellular carcinoma

2016 ◽  
Vol 54 (12) ◽  
Author(s):  
Martin Mžik ◽  
Marcela Chmelařová ◽  
Stanislav John ◽  
Jan Laco ◽  
Ondřej Slabý ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Promoter Methylation ◽  
Mrna Level ◽  
Methylation Status ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Aberrant Methylation ◽  
Suppressor Genes ◽  
Tissue Samples ◽  
Differentially Methylated Genes

AbstractBackground:Aberrant hypermethylation of tumour suppressor genes (TSGs) occurring in hepatocellular carcinoma (HCC) could provide a mean of molecular characterisation of this cancer. The aim of this study was to investigate promoter methylation and gene expression of selected TSGs in HCC to identify candidate genes for further validation as potential biomarkers.Methods:Methylation-specific multiplex ligation-dependent probe amplification method was used to measure the methylation status of 25 TSGs in 49 HCC samples and 36 corresponding non-cancerous liver tissue samples. Relative expression of the differentially methylated genes was assessed at the mRNA level using quantitative PCR.Results:We observed a significantly higher methylation in genesConclusions:HCC evince aberrant promoter methylation of

scholarly journals Evidence for the presence of two tumour-suppressor genes for hepatocellular carcinoma on chromosome 13q

1995 ◽  
Vol 72 (2) ◽  
pp. 383-385 ◽  
Author(s):  
T Kuroki ◽  
Y Fujiwara ◽  
S Nakamori ◽  
S Imaoka ◽  
T Kanematsu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Suppressor Genes ◽  
Chromosome 13Q

scholarly journals Methylation Analysis of Several Tumour Suppressor Genes Shows a Low Frequency of Methylation ofCDKN2AandRARBin Uveal Melanomas

2003 ◽  
Vol 4 (3) ◽  
pp. 329-336 ◽  
Author(s):  
Michael Zeschnigk ◽  
Frank Tschentscher ◽  
Christina Lich ◽  
Birgit Brandt ◽  
Bernhard Horsthemke ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Metastatic Disease ◽  
Kinase Inhibitor ◽  
Tumour Suppressor ◽  
Chromosome 3 ◽  
Tumour Suppressor Genes ◽  
Aberrant Methylation ◽  
Causative Role ◽  
Suppressor Genes ◽  
Monosomy 3

We have investigated the frequency of methylation of several tumour suppressor genes in uveal melanoma. As the loss of one copy of chromosome 3 (monosomy 3), which is found in about half of these tumours, is tightly associated with metastatic disease, a special emphasis was laid on genes located on this chromosome, including the fragile histidine triad (FHIT), von Hippel–Lindau (VHL), β-catenin (CTNNB1), activated leukocyte cell adhesion molecule (ALCAM) and retinoic acid receptor-β2 (RARB) genes. In addition, the methylation patterns of the CpG-rich regions 5′ of the E-cadherin (CDH1), p16/cyclin-dependent kinase inhibitor 2 A (CDKN2A) and retinoblastoma (RB1) genes were analysed by bisulphite genomic sequencing or methylation-specific PCR (MSP). Furthermore, the SNRPN andD15S63loci, which are located in the imprinted region of chromosome 15, were included in the study. Aberrant methylation was detected in nine of 40 tumours analysed: The imprintedSNRPNandD15S63loci were hypermethylated in three tumours, all of which retained both copies of chromosome 3. MethylatedRARBalleles were detected in three tumours, whereas in three other tumoursCDKN2Awas found to be methylated. As we did not find RARB and CDKN2A preferentially methylated in tumours with monosomy 3, which is a significant predictor of metastatic disease, we suggest that these genes may play a causative role in the formation of uveal melanoma but not in the development of metastases.

Prognostic Significance of Promoter Methylation of Multiple Genes in Germinal Center Hyperplasia (GCH) and Lymphomas of Germinal Center Origin.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3950-3950
Author(s):  
Jose M Paz-Carreira ◽  
Arantxa Garcia-Rivero ◽  
Raquel Losada ◽  
Jose C Mendez ◽  
Manuel Albors ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Suppressor ◽  
Promoter Methylation ◽  
Germinal Center ◽  
Tumor Suppressor Genes ◽  
Methylation Status ◽  
Prognostic Significance ◽  
Promoter Hypermethylation ◽  
Aberrant Methylation ◽  
Suppressor Genes

Abstract Abstract 3950 Poster Board III-886 INTRODUCTION Germinal centers (GC) are unique sites in peripheral lymphoid tissue where clonal selection of B cells takes place. GC have been known to be a major source of B-cell lymphomas, including follicular (FL) and diffuse large cell (DLCL). DNA methylation of tumor-suppressor genes is a mechanism of gene silencing involved in the pathogenesis of FL and DLCBLs. Much less is known about the role of methylation in GCH. We determined the methylation status of 5 tumor-suppressor genes in 50 patients with lymphoma of GC origin and 50 GCH in order to find any differences between the pathological and the physiological state as well as its prognostic significance. MATERIAL AND METHODS. Genomic DNA extracted from paraffin-embedded samples of 30 DLCL, 20 FL and 50 GCH were analyzed by methylation-specific polymerase chain-reaction to determine promoter hypermethylation of DAP-k, SHP1, Rarβ, p14 and MGMT. Methylation status of each gene was correlated with clinicopathological status. Overall survival (OS) rates were calculated by the Kaplan-Meier method and differences were compared with the log-rank test. RESULTS. Median age was 65 in patients with lymphoma and 19 for GCH. Sex distribution was similar in all entities (60% females). Both lymphoma groups were balanced with respect to the presence of B symptoms, bulky disease, bone marrow infiltration, advanced stage and high IPI/FLIPI. DAP-k promoter methylation was present in more patients with lymphoma (89 and 87%) than with BFH (37%) p<0.0001. RaRB was methylated with higher frequency in FL (60%) than in DLCL (23%) and FH (12%) p<0.0001. SHP1 was more frequently methylated in FL (67%) and GCH (58%) than in DLCL (20%) p=0.01. Promoter hypermethylation of SHP1 was significantly associated with longer OS (p=0.021). Methylation of RaRB, p14 and MGMT were associated with shortened OS but the differences were not statistically significant. Those patients with DAPK methylated live longer but not significantly. In multivariate analysis hypermethylation of none of the genes studied remained an independent prognostic factor. CONCLUSIONS. Inactivation of DAP-K, and Rarβ is present in GC lymphomas with significantly higher frequency than in BFH. Thus, it may have pathogenic significance. SHP1 is methylated more frequently if FL and BFH than in DLCL, therefore that gene may be associated with aggressive disease. Methylation of DAP-k, SHP1, Rarβ, p14 and MGMT has no significant impact on overall survival. Markers for aberrant methylation may represent a promising way to monitor the onset and progression of malignancies but more extensive and prospective trials are needed to precisely define its role. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Aberrant Methylation Status of Tumour Suppressor Genes in Ovarian Cancer Tissue and Paired Plasma Samples

2019 ◽  
Vol 20 (17) ◽  
pp. 4119 ◽  
Author(s):  
Dana Dvorská ◽  
Dušan Braný ◽  
Bálint Nagy ◽  
Marián Grendár ◽  
Robert Poka ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Aberrant Methylation ◽  
Potential Candidate ◽  
Plasma Samples ◽  
Cdh1 Gene ◽  
Suppressor Genes ◽  
Non Invasive ◽  
Malignant Lesions

Ovarian cancer is a highly heterogeneous disease and its formation is affected by many epidemiological factors. It has typical lack of early signs and symptoms, and almost 70% of ovarian cancers are diagnosed in advanced stages. Robust, early and non-invasive ovarian cancer diagnosis will certainly be beneficial. Herein we analysed the regulatory sequence methylation profiles of the RASSF1, PTEN, CDH1 and PAX1 tumour suppressor genes by pyrosequencing in healthy, benign and malignant ovarian tissues, and corresponding plasma samples. We recorded statistically significant higher methylation levels (p < 0.05) in the CDH1 and PAX1 genes in malignant tissues than in controls (39.06 ± 18.78 versus 24.22 ± 6.93; 13.55 ± 10.65 versus 5.73 ± 2.19). Higher values in the CDH1 gene were also found in plasma samples (22.25 ± 14.13 versus 46.42 ± 20.91). A similar methylation pattern with positive correlation between plasma and benign lesions was noted in the CDH1 gene (r = 0.886, p = 0.019) and malignant lesions in the PAX1 gene (r = 0.771, p < 0.001). The random forest algorithm combining methylation indices of all four genes and age determined 0.932 AUC (area under the receiver operating characteristic (ROC) curve) prediction power in the model classifying malignant lesions and controls. Our study results indicate the effects of methylation changes in ovarian cancer development and suggest that the CDH1 gene is a potential candidate for non-invasive diagnosis of ovarian cancer.

Novel Tumour Suppressor Genes Sorbs3 and Sh2d4a Repress Il-6 Signalling in Hepatocellular Carcinoma

2016 ◽  
Vol 64 (2) ◽  
pp. S158
Author(s):  
C. Ploeger ◽  
N. Waldburger ◽  
A. Fraas ◽  
B. Goeppert ◽  
S. Pusch ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Suppressor Genes
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